Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  DNA topoisomerase 1  

UniProtKB / Swiss-Prot ID :  TOP1_HUMAN

Gene Name (Synonyms) : 
TOP1  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Nucleus, nucleolus. Nucleus, nucleoplasm. Note=Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumolyated forms found in both nucleoplasm and nucleoli. 

Protein Function :  Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand than undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. 

Protein Sequence MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKKHKEKEKTKHK...
Predicted Secondary Structure CCCCCEECCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCHHHC...
Protein Variant
LocationDescription
214G -> S (in dbSNP:rs6029542). VAR_052592
326K -> R (in breast cancer; somaticmutation).
370M -> T (in CPT-resistant leukemia). VAR_010666
533D -> G (in CPT-resistant leukemia). VAR_007530
722N -> S (in CPT-resistant leukemia). VAR_010667
729T -> A (in CPT-resistant lung cancer). VAR_007531
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
2N-acetylserine---MSGDHL
---CCCCCE
53.58HPRD
Link-
2N-acetylserine.---MSGDHL
---CCCCCE
53.58UniProtKB
Link-
2Phosphoserine---MSGDHL
---CCCCCE
53.58HPRD
Link-
2Phosphoserine---MSGDHL
---CCCCCE
53.58Phosphositeplus
Link-
2Phosphoserine---MSGDHL
---CCCCCE
53.58SysPTM
Link-
10PhosphoserineLHNDSQIEA
EECCCCCCC
38.07HPRD
Link-
10PhosphoserineLHNDSQIEA
EECCCCCCC
38.07PhosphoELM
Link-
10PhosphoserineLHNDSQIEA
EECCCCCCC
38.07Phosphositeplus
Link-
10PhosphoserineLHNDSQIEA
EECCCCCCC
38.07SysPTM
Link-
21PhosphoserineRLNDSHKHK
CCCCCCCCC
33.10HPRD
Link-
21PhosphoserineRLNDSHKHK
CCCCCCCCC
33.10Phosphositeplus
Link-
57PhosphoserineEHKDSEKKH
CCCCCCCCC
57.00HPRD
Link-
57PhosphoserineEHKDSEKKH
CCCCCCCCC
57.00Phosphositeplus
Link-
73PhosphoserineHKDGSSEKH
HCCCCCCCC
45.52HPRD
Link-
73PhosphoserineHKDGSSEKH
HCCCCCCCC
45.52Phosphositeplus
Link-
103Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)DAKIKKEKE
CCCCCCCCC
54.92Phosphositeplus
Link-
111PhosphoserineENGFSSPPQ
CCCCCCCHH
43.25HPRD
Link-
112PhosphoserineNGFSSPPQI
CCCCCCHHH
38.04HPRD
Link-
112PhosphoserineNGFSSPPQI
CCCCCCHHH
38.04PhosphoELM
Link-
112PhosphoserineNGFSSPPQI
CCCCCCHHH
38.04Phosphositeplus
Link-
112Phosphoserine.NGFSSPPQI
CCCCCCHHH
38.04UniProtKB
Link-
117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)PPQIKDEPE
CHHHCCCCC
51.28HPRD
Link-
117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)PPQIKDEPE
CHHHCCCCC
51.28Phosphositeplus
Link-
117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO).PPQIKDEPE
CHHHCCCCC
51.28UniProtKB
Link-
123noneEPEDDGYFV
CCCCCCCCC
52.62HPRD
Link-
125PhosphotyrosineEDDGYFVPP
CCCCCCCCC
14.38HPRD
Link-
146noneEDDADYKPK
CCCCCCCCC
60.01HPRD
Link-
153Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)PKKIKTEDT
CCCCCCCCC
55.53Phosphositeplus
Link-
170noneEEEEDGKLK
CCCCCCCCC
63.91HPRD
Link-
170noneEEEEDGKLK
CCCCCCCCC
63.91HPRD
Link-
172N6-acetyllysineEEDGKLKKP
CCCCCCCCC
70.25HPRD
Link-
172N6-acetyllysineEEDGKLKKP
CCCCCCCCC
70.25Phosphositeplus
Link-
223Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FLEHKGPVF
EEEECCCCC
56.38Phosphositeplus
Link
239Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)PENVKFYYD
CCCCEEEEC
38.95Phosphositeplus
Link
245Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)YYDGKVMKL
EECCCCCCC
35.94Phosphositeplus
Link
252Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)KLSPKAEEV
CCCHHHHHH
66.12Phosphositeplus
Link
268PhosphotyrosineLDHEYTTKE
HHHHHHHHH
19.11Phosphositeplus
Link
268Phosphotyrosine (Abl)LDHEYTTKE
HHHHHHHHH
19.11PhosphoELM
Link
280Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)KNFFKDWRK
HHHHHHHHH
52.85Phosphositeplus
Link
280N6-acetyllysineKNFFKDWRK
HHHHHHHHH
52.85HPRD
Link
280N6-acetyllysineKNFFKDWRK
HHHHHHHHH
52.85Phosphositeplus
Link
280N6-acetyllysine.KNFFKDWRK
HHHHHHHHH
52.85UniProtKB
Link
298PhosphoserineITNLSKCDF
HCCHHCCCH
33.05HPRD
Link
298PhosphoserineITNLSKCDF
HCCHHCCCH
33.05Phosphositeplus
Link
326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)EEKLKIKEE
HHHHHHHHH
63.90Phosphositeplus
Link
354Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)IANFKIEPP
EEEEEECCC
46.06Phosphositeplus
Link
394PhosphoserineAKVPSPPPG
CCCCCCCCC
53.69Phosphositeplus
Link
400Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)PPGHKWKEV
CCCCCCCEE
66.91Phosphositeplus
Link
426PhosphotyrosineGSIKYIMLN
CCEEEEEEC
7.01HPRD
Link
426PhosphotyrosineGSIKYIMLN
CCEEEEEEC
7.01Phosphositeplus
Link
432PhosphoserineMLNPSSRIK
EECCCCCCC
31.04HPRD
Link
444PhosphotyrosineDWQKYETAR
HHHHHHHHH
11.92Phosphositeplus
Link
549Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)KRVFKNLQL
HHHHHHHHH
54.62Phosphositeplus
Link
558Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FMENKQPED
HHCCCCCCC
54.66Phosphositeplus
Link
587Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)GLTAKVFRT
CCEEEEEEE
36.35Phosphositeplus
Link
603Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)QQQLKELTA
HHHHHHHCC
46.47Phosphositeplus
Link
615Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)NIPAKILSY
CHHHHHHHH
38.53Phosphositeplus
Link
642Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)KTFEKSMMN
CCHHHHHHH
39.19Phosphositeplus
Link-
712Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)REENKQIAL
HHHCCEEEE
46.49Phosphositeplus
Link-
723PhosphotyrosineSKLNYLDPR
CCCEEECCE
23.95Phosphositeplus
Link
742Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)VPIEKIYNK
CCHHHHHHH
51.73Phosphositeplus
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
P53_HUMANphysical interactionMINT-16028MINT8639538
NUCL_HUMANphysical interactionMINT-73226MINT9512561
APLF_HUMANphysical interactionMINT-4790124MINT17396150
TOPB1_HUMANphysical interactionMINT-3379396MINT17006541
HNRPR_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
NPM_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
HNRPC_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
HNRPU_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
TOP2A_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
ROA1_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
PARP1_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
DDX17_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
DHX9_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
ELAV1_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
HNRPK_HUMANphysical interaction
physical interaction
EBI-876685
EBI-876476
intact15848144
15848144
ROA2_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
PRP8_HUMANphysical interaction
physical interaction
EBI-876685
EBI-876315
intact15848144
15848144
RU2A_HUMANphysical interaction
physical interaction
EBI-876685
EBI-876315
intact15848144
15848144
PRKDC_HUMANphysical interaction
physical interaction
EBI-876685
EBI-876315
intact15848144
15848144
DDX21_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
SFPQ_HUMANphysical interaction
physical interaction
EBI-876685
EBI-876476
intact15848144
15848144
U520_HUMANphysical interaction
physical interaction
EBI-876685
EBI-876315
intact15848144
15848144
H12_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
NONO_HUMANphysical interaction
physical interaction
EBI-876685
EBI-876476
intact15848144
15848144
SFRS1_HUMANphysical interaction
physical interaction
physical interaction
EBI-876685
EBI-876315
EBI-876
intact15848144
15848144
15848144
DDX5_HUMANphysical interaction
physical interaction
EBI-876315
EBI-876476
intact15848144
15848144
DDX23_HUMANphysical interactionEBI-876315
intact15848144
KI67_HUMANphysical interactionEBI-876315
intact15848144
TCOF_HUMANphysical interactionEBI-876315
intact15848144
H1X_HUMANphysical interaction
physical interaction
EBI-876315
EBI-876476
intact15848144
15848144
U5S1_HUMANphysical interactionEBI-876315
intact15848144
NOL1_HUMANphysical interactionEBI-876315
intact15848144
NUCL_HUMANphysical interaction
physical interaction
EBI-876315
EBI-876476
intact15848144
15848144
NAT8B_HUMANphysical interactionEBI-876476
intact15848144
FBRL_HUMANphysical interactionEBI-876476
intact15848144
ROA3_HUMANphysical interactionEBI-876476
intact15848144
SF3B1_HUMANphysical interactionEBI-876476
intact15848144
NAT10_HUMANphysical interactionEBI-876476
intact15848144
HNRPL_HUMANphysical interactionEBI-876476
intact15848144
CSK21_HUMANin vitro
in vivo
HPRD:00535HPRD2998765
TOP1_HUMANin vitroHPRD:00535HPRD9756848
BTBD2_HUMANENSP00000354522STRING
SFRS1_HUMANENSP00000354522STRING
BTBD1_HUMANENSP00000354522STRING
SUMO1_HUMANENSP00000354522STRING
P53_HUMANENSP00000354522STRING
PRKDC_HUMANENSP00000354522STRING
NUCL_HUMANENSP00000354522STRING
KU86_HUMANENSP00000354522STRING
KU86_HUMANENSP00000354522STRING
KU86_HUMANENSP00000354522STRING
UBC9_HUMANENSP00000354522STRING
KU70_HUMANENSP00000354522STRING
KU70_HUMANENSP00000354522STRING
TOPRS_HUMANENSP00000354522STRING
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
DrugBank
DB00762Irinotecan
DB04967Lucanthone
DB05630Sodium stibogluconate
DB01030Topotecan
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280, AND MASS SPECTROMETRY.
Phosphorylation
ReferencePubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, AND MASSSPECTROMETRY.
Sumoylation
ReferencePubMed
"Sumoylation of topoisomerase I is involved in its partitioningbetween nucleoli and nucleoplasm and its clearing from nucleoli inresponse to camptothecin.";
Rallabhandi P., Hashimoto K., Mo Y.-Y., Beck W.T., Moitra P.K.,D'Arpa P.;
J. Biol. Chem. 277:40020-40026(2002).
Cited for: SUMOYLATION AT LYS-117, SUBCELLULAR LOCATION, AND MUTAGENESIS OFLYS-103; LYS-117; LYS-153 AND TYR-723.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures